Topiramate. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of epilepsy

Abstract

Topiramate is a sulphamate-substituted monosaccharide derived from D-fructose and is structurally unrelated to other antiepileptic drugs. It acts by multiple mechanisms that suggest it may be effective in several types of epilepsy. In double-blind placebo-controlled trials, add-on therapy with topiramate 400 to 1000 mg/day reduces the seizure rate by > or = 50% in 35 to 52% of adult patients with resistant partial epilepsy (with or without secondarily generalised seizures) compared with 0 to 19% of placebo recipients; a 200 mg/day dosage was less effective. Topiramate has also been shown to be superior in efficacy to placebo in well controlled trials in patients with generalised tonic-clonic seizures, Lennox-Gastaut syndrome and in paediatric patients with partial epilepsy. Efficacy has been maintained for 7 years and some patients may also be satisfactorily treated with topiramate monotherapy. Further study is needed to follow up on the promising results of topiramate use in other paediatric epilepsies. Adverse CNS events are the most common untoward effects during topiramate therapy and are most likely to lead to withdrawal of the drug. However, most adverse events are mild to moderate in severity and lessen with continued drug therapy. In clinical trials, most adverse events which were dose limiting or led to discontinuation of treatment occurred during the titration phase. The overall incidence of adverse events may be reduced by slower upward dosage titration. In summary, topiramate appears to be a suitable agent for add-on therapy in adult patients with partial epilepsy. Preliminary reports support the use of add-on topiramate in adults with generalised epilepsy, in childhood epilepsies and in patients with Lennox-Gastaut syndrome, as well as the use of topiramate monotherapy in patients with partial epilepsy. Thus, topiramate can be considered an important new drug for the management of patients with refractory epilepsy.